Subcellular biochemical & anatomical studies will be carried out to provide a unique insight into the neurotransmitter uptake process of blood vessels from hypertensive rats. Our preliminary biochemical work points to a reduction in the in vitro uptake of radioactive norepinephrine, H3-NE, by portal-mesenteric veins and carotid arteries of spontaneously hypertensive rats, SHR, and rats with neurogenic hypertension induced by sinoaortic denervation, SAD. Anatomical studies of storage vesicles and nerve terminal distribution will be correlated with in vitro uptake to H3-NE by vascular subcellular fractions. It will be determined whether reduced H3-NE incorporation is widespread in the vasular system of adult hypertensive rats and whether the incorporation defect is present early in the course of neurogenic hypertensives and in the pre-hypertensive stage of genetic hypertension. The underlying mechanism(s) for reduced He-NE uptake will be investigated with respect to the ionic environment, degradative enzyme activity and membrane transport systems of blood vessels.